1. Field of the Invention
The invention relates to novel hexahydropyridazine-3-carboxylic acid hydrazide or hydrazone derivatives, to the combinatorial libraries containing them, to the preparation thereof, to the use thereof as medicinal products, in particular as cathepsin K inhibitors, and also to the pharmaceutical compositions containing them.
2. Description of the Art
Metabolic enzymes such as proteases or kinases are enzymes that are widely distributed in the animal kingdom. By way of nonexhaustive examples, mention may be made, as bibliographical references for proteases, of the documents: “Methods in Enzymology XLII (1975)” and “Journal of Medicinal Chemistry” vol. 43 no3 (D. Leung, G. Abbenante and D. P. Fairlie) and for kinases, the document: “Methods in Enzymology”, Vol 80 (1981) (Academic Press Inc.).
Among the proteases capable of selectively catalyzing the hydrolysis of polypeptide bonds, mention may be made of the four main classes: aspartic protease, serine protease, cysteine protease and metalloprotease.
Aspartic proteases that may be mentioned include in particular HIV-1 protease, renin, plasmepsins and cathepsin D.
Serine proteases that may be mentioned include in particular thrombin, factor Xa, elastase, tryptase, “convertase complements” and hepatitis C NS3 protease.
Among the cysteine proteases, there are three structurally distinct groups: the papain and cathepsin group, the ICE group (caspases) and the picornaviral group (similar to the serine proteases, in which the serine is replaced with a cysteine).
Thus, mention may in particular be made of cathepsin K, cathepsin B, cathepsin L, cathepsin S, caspases, rhinovirus 3C protease, and the papains and calpains.
Metalloproteases that may be mentioned include in particular angiotensin-converting enzyme, neutral endopeptidase and a mixture of the two, matrix metalloprotease and tumor necrosis factor-α-converting enzyme.
These kinase or protease enzymes are involved in intercellular and intracellular catabolization and communication processes: they play an important role in a large number of diseases in different fields, such as in particular the cardiovascular field, oncology, the central nervous system, inflammation, osteoporosis and also infectious, parasitic, fungal or viral diseases. For this reason, these proteins are targets of great interest for pharmaceutical research.
All of the aforementioned references are incorporated herein by reference in their entirety.